Affinage

CD19

B-lymphocyte antigen CD19 · UniProt P15391

Length
556 aa
Mass
61.1 kDa
Annotated
2026-06-09
100 papers in source corpus 18 papers cited in narrative 18 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 10/10 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CD19 is a B-cell transmembrane co-receptor that lowers the antigen-receptor activation threshold and amplifies B-cell signaling, integrating multiple inputs to govern B-cell development, germinal center maturation, and humoral immunity (PMID:7542009, PMID:12387743). On the cell surface it assembles into a multimolecular complex with complement receptor CR2 (CD21) and the tetraspanin TAPA-1 (CD81); cross-linking CD19 to membrane immunoglobulin reduces by two orders of magnitude the number of receptors that must be engaged to activate phospholipase C and drive DNA synthesis, and the CR2-CD19 interaction is required for germinal center B-cell survival and secondary antibody responses (PMID:7542009, PMID:19706534). Signal amplification depends on a Src-family kinase loop in which Lyn phosphorylates CD19, which in turn sustains phosphorylation of Fyn and other Src-family PTKs to drive a hyperresponsive, autoimmune-prone phenotype (PMID:11509585). Phosphorylated CD19 couples to PI3K, promoting efficient and sustained Akt activation, physically associates with Btk to maintain it in an active state for intracellular Ca2+ responses, and reciprocally regulates Vav phosphorylation to tune BCR signaling thresholds (PMID:9371816, PMID:11042164, PMID:12023340). The cytoplasmic tyrosines Y482 and Y513 are essential for all CD19 functions in vivo, including B1 and marginal zone B-cell differentiation, T-dependent and -independent antibody responses, and germinal-center cell-cycle progression (PMID:12387743), and the cytoplasmic signaling domain confers growth suppression when CD19 is expressed in myeloma cells (PMID:10552966). Beyond the BCR, CD19 is required for TLR9-induced activation, becoming phosphorylated via MYD88/PYK2/LYN to recruit PI3K and activate Btk and Akt (PMID:26478008). CD19 transcription is positively controlled by an Mst1-TEAD2 axis acting on the cd19 3'UTR and by a WASP/Dock8 pathway, both of which feed back to support CD19-mediated Btk signaling and BCR clustering (PMID:29296937, PMID:29472447). Human CD19 deficiency impairs somatic hypermutation and selection of immunoglobulin reactivity in memory B cells (PMID:24418477). Surface localization requires CD81 binding: exon 2 alterations prevent CD81 association, trap CD19 with calnexin in the ER as a high-mannose glycoform, and abolish surface expression (PMID:30104252). The extracellular domain presents a conformational FMC63 epitope spanning exon 3- and exon 4-encoded loops, structurally defined by cryo-EM, and CD19 antigen density and glycosylation state critically modulate CAR T-cell cytolysis, trogocytosis, and antigen escape (PMID:30104252, PMID:35690611, PMID:36867678, PMID:31702909, PMID:35362043).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1995 High

    Established CD19 as a threshold-setting co-receptor by defining its surface complex and signaling couplings, answering how B cells could be activated by far fewer antigen-receptor engagements.

    Evidence Biochemical co-association, crosslinking, and signaling assays (PLC, DNA synthesis, Ca2+) in B cells

    PMID:7542009

    Open questions at the time
    • Stoichiometry and dynamics of the CD19/CD21/CD81 complex not resolved
    • Direct kinase-substrate steps inferred rather than fully reconstituted
  2. 1997 High

    Showed CD19 and CD22 reciprocally control Vav phosphorylation, providing a molecular rheostat for adjusting BCR signaling thresholds.

    Evidence BCR crosslinking in CD19-/- and CD22-/- mouse B cells with Vav phospho-immunoblotting

    PMID:9371816

    Open questions at the time
    • Direct versus indirect link between CD19 and Vav not defined
    • Downstream consequences of altered Vav phosphorylation not quantified
  3. 1999 High

    Demonstrated that CD19 signaling can suppress growth in non-B-lineage myeloma cells, revealing a context-dependent growth-regulatory function dependent on the cytoplasmic domain.

    Evidence CD19 transfection of myeloma cells with cytoplasmic truncation controls; in vitro growth and SCID xenograft assays

    PMID:10552966

    Open questions at the time
    • Effector pathway of growth suppression not identified
    • Relevance to normal plasma cells unaddressed
  4. 2001 High

    Placed CD19 upstream of PI3K-Akt survival signaling and within a Lyn-dependent Src-family amplification loop, mechanistically linking the co-receptor to hyperresponsiveness and autoimmunity.

    Evidence CD19-/- B cells and CD19/Lyn double-knockout mice; Akt kinase assays, Ca2+ responses, phospho-immunoblots, autoimmunity readouts

    PMID:11042164 PMID:11509585

    Open questions at the time
    • Direct PI3K recruitment site on CD19 not defined in these studies
    • How Lyn-phosphorylated CD19 amplifies other Src-family PTKs mechanistically unresolved
  5. 2002 High

    Identified the essential cytoplasmic tyrosines and the physical CD19-Btk association, establishing the specific signaling residues and a Btk-maintenance mechanism required for in vivo B-cell function.

    Evidence CD19-/- mice reconstituted with Y482/Y513 mutants; co-IP of Btk with CD19; CD19-/- x Xid compound mice; Ca2+ and kinase assays

    PMID:12023340 PMID:12387743

    Open questions at the time
    • Identity of effectors recruited specifically to Y482 versus Y513 not delineated
    • Mechanism by which CD19 sustains active Btk not structurally defined
  6. 2003 High

    Extended CD19 function to early B-cell development, showing it promotes the pro-B to pre-B transition via pre-BCR-driven proliferation.

    Evidence CD19-/- mice; BrdU/cell-cycle analysis; IL-7 pre-B cultures; Btk and ERK activation assays

    PMID:14634103

    Open questions at the time
    • Whether pre-BCR-CD19 coupling uses the same complex as mature BCR not established
  7. 2009 High

    Demonstrated that CR2 must signal through CD19 for coreceptor activity in humoral immunity, separating ligand binding from signaling output.

    Evidence Cr2-Delta/Delta-gfp knockin mice with separation-of-function mutation; germinal center, antibody titer, and memory assays

    PMID:19706534

    Open questions at the time
    • Molecular interface enabling CR2-to-CD19 signal transfer not defined
  8. 2014 Medium

    Linked human CD19 signaling to the somatic hypermutation machinery, showing it regulates AID, UNG2, and mismatch repair activities during memory B-cell selection.

    Evidence CD19-deficient patient B cells; SHM and immunoglobulin transcript analysis; flow cytometry

    PMID:24418477

    Open questions at the time
    • Transcriptional pathway from CD19 to DNA-repair gene regulation not mapped
    • Single patient cohort
  9. 2015 High

    Showed CD19 is also required for TLR9 signaling, integrating innate and antigen-receptor pathways through a distinct MYD88/PYK2/LYN-initiated phosphorylation route.

    Evidence CD19-deficient patient B cells, phospho-flow, co-IP, knockdown lines, PI3K/AKT/BTK inhibitors

    PMID:26478008

    Open questions at the time
    • How TLR9-driven CD19 phosphorylation differs in kinetics/sites from BCR-driven phosphorylation not fully resolved
  10. 2016 Medium

    Identified transcriptional control of CD19 by an Mst1-TEAD2 axis and a WASP/Dock8 pathway, showing CD19 abundance is actively set to tune BCR signaling and B-cell clustering.

    Evidence Mst1 and Dock8 knockout mice and patient cells; TIRF/confocal imaging; TEAD2 3'UTR binding; phospho-CD19/Btk assays

    PMID:29296937 PMID:29472447

    Open questions at the time
    • Single-lab transcriptional mechanisms
    • Direct versus indirect TEAD2 and WASP effects on cd19 not fully separated
  11. 2018 High

    Defined CD81-dependent surface trafficking of CD19 and the molecular basis of exon 2-driven CAR T resistance as ER misfolding rather than epitope loss.

    Evidence VSVg-tagged exon 2 variants; pulse-chase glycosylation, ER colocalization, MS interactome (calnexin), ADC killing assays

    PMID:30104252

    Open questions at the time
    • Structural basis of CD19-CD81 association not resolved
    • Folding intermediates and quality-control kinetics not detailed
  12. 2019 High

    Mapped the conformational FMC63 epitope to exon 3/4-encoded loops and showed N-glycosylation is dispensable for antibody binding, informing CAR and antibody recognition.

    Evidence Saturation mutagenesis library, yeast display, flow cytometric epitope mapping, thermal stability selection

    PMID:31702909

    Open questions at the time
    • Native membrane context of the epitope not addressed
    • Relationship of epitope loops to coreceptor signaling untested
  13. 2022 Medium

    Revealed post-translational and trafficking mechanisms of antigen escape: SPPL3-dependent hyperglycosylation blunts CAR T killing, and CAR-induced lysosomal degradation of CD19 yields transiently antigen-negative cells.

    Evidence SPPL3 loss/gain in B cells with CAR T cytotoxicity assays; CAR-T19 vs STAb-T19 cocultures with lysosome inhibition, synapse imaging, and PDX models

    PMID:35362043 PMID:35690611

    Open questions at the time
    • Single-lab pre-clinical models
    • In vivo clinical relevance of SPPL3-driven escape not established
    • Reversibility kinetics of CD19 downmodulation not fully quantified
  14. 2023 High

    Provided cryo-EM structures of CD19 bound to clinically used scFvs and showed affinity tuning dictates antigen-density thresholds and trogocytosis, connecting CD19 structure to CAR T efficacy.

    Evidence Cryo-EM, molecular dynamics, affinity-variant CARs, cytolysis assays at varying antigen densities, trogocytosis assays

    PMID:36867678

    Open questions at the time
    • Structure of full-length CD19 in its native coreceptor complex not determined
    • In vivo correlation of affinity tuning with durable response not shown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the CD19 cytoplasmic signaling module, its transcriptional regulators, and its CD81-dependent trafficking are mechanistically integrated within the native coreceptor complex at atomic resolution remains unresolved.
  • No structure of the assembled CD19/CD21/CD81 signaling complex
  • Direct CD19 cytoplasmic-domain interactome incompletely defined
  • Causal hierarchy among transcriptional inputs (Mst1-TEAD2, WASP/Dock8) unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 3 GO:0060090 molecular adaptor activity 3 GO:0098772 molecular function regulator activity 2
Localization
GO:0005886 plasma membrane 2 GO:0005783 endoplasmic reticulum 1
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-168256 Immune System 3
Partners
BTKCALNEXINCD21CD81CR2LYNVAV
Complex memberships
CD19/CD21(CR2)/CD81(TAPA-1) B-cell coreceptor complex

Evidence

Reading pass · 18 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 CD19 forms a multimolecular complex on the B cell surface with complement receptor CR2 (CD21) and tetraspanin TAPA-1 (CD81). Cross-linking CD19 to membrane immunoglobulin (mIg) lowers by two orders of magnitude the number of mIg molecules that must be ligated to activate phospholipase C or induce DNA synthesis. CD19 is coupled via protein tyrosine kinases to PLC and PI3-kinase and interacts with the Src-type nonreceptor PTK Lyn. Biochemical co-association studies, crosslinking experiments, signaling assays (PLC activation, DNA synthesis, Ca2+ responses) Annual review of immunology High 7542009
1997 CD19 and CD22 reciprocally regulate tyrosine phosphorylation of Vav protein during B lymphocyte BCR signaling. CD19 crosslinking is more efficient than BCR crosslinking at inducing Vav phosphorylation; simultaneous crosslinking of CD19 with the BCR resulted in decreased Vav phosphorylation when CD22 was expressed. This differential regulation of Vav by CD19 and CD22 provides a molecular mechanism for adjusting BCR signaling thresholds. BCR crosslinking in CD22-deficient and CD19-deficient mouse B cells, immunoblotting for Vav tyrosine phosphorylation Proceedings of the National Academy of Sciences of the United States of America High 9371816
2001 CD19 is necessary for efficient activation of Akt kinase following BCR or Igβ crosslinking in B cells. In the absence of CD19, Akt kinase activity is reduced and transient. Coligation of CD19 with surface immunoglobulin leads to augmented Akt activity in a dose-dependent manner, placing CD19 as a key regulator of PI3K-dependent Akt activity and cell survival signaling. CD19-deficient B-lymphoma cell lines and CD19-deficient mouse splenic B cells; Akt kinase activity assays after BCR/Igβ crosslinking The Journal of biological chemistry High 11042164
2001 CD19 establishes a Src-family kinase activation loop requiring Lyn for CD19 phosphorylation. In Lyn-deficient mice, CD19 deficiency suppresses hyperresponsive B cell phenotype and autoimmunity (serum autoantibodies and glomerulonephritis). CD19 deficiency in Lyn-/- mice reduced Fyn and other cellular protein tyrosine phosphorylation following BCR ligation while Syk phosphorylation remained normal, demonstrating that CD19 amplifies signals through Src family PTKs other than Lyn. Double-knockout mice (CD19/Lyn-/-); BCR-induced Ca2+ responses, tyrosine phosphorylation immunoblots, humoral immune response assays Journal of immunology (Baltimore, Md. : 1950) High 11509585
2002 CD19 cytoplasmic tyrosines Y482 and Y513 are essential for all CD19 functions in vivo, including B1 and marginal zone B cell differentiation, T-dependent and -independent antibody responses, and germinal center B cell maturation/cell cycle progression. Mutation of these residues blocks germinal center maturation associated with retarded cell cycle progression. CD19-knockout mice expressing transgenic CD19 constructs with tyrosine mutations; in vivo immunization, flow cytometry, cell cycle analysis Immunity High 12387743
2002 Bruton's tyrosine kinase (Btk) physically associates with CD19 following BCR engagement in B cells. CD19 expression maintains Btk in an activated state following BCR engagement but is not required for initial Btk phosphorylation. CD19-induced intracellular Ca2+ responses require downstream Btk function. CD19 and Btk regulate partially overlapping but also independent signaling pathways. Co-immunoprecipitation of Btk with CD19 in A20 B cells; CD19-/- and Xid (Btk-mutant) compound mouse models; Ca2+ flux assays; PI3K and Akt activation assays Journal of immunology (Baltimore, Md. : 1950) High 12023340
2003 CD19 facilitates the pro-B to pre-B cell transition by promoting proliferation downstream of pre-BCR signaling. In CD19-/- mice, the large cycling pre-B cell fraction is reduced. Signaling through the pre-BCR is impaired in the absence of CD19, as shown by reduced activation of Bruton's tyrosine kinase and ERK/MAPK. CD19-/- mouse model; sublethal irradiation reconstitution experiments; BrdU labeling and cell cycle analysis; IL-7-dependent pre-B cell cultures; Btk and ERK activation assays Journal of immunology (Baltimore, Md. : 1950) High 14634103
2009 CD21 (CR2) interaction with CD19 is necessary for coreceptor activity in humoral immunity. Knockin mice expressing mutant CR2 receptors that bind C3 ligands but cannot signal through CD19 showed significantly diminished germinal center B cell survival and secondary antibody titers, but B memory formation was less impaired than in complete CR deficiency. Knockin mouse model (Cr2-Delta/Delta-gfp); germinal center B cell survival analysis, antibody titer measurements, B memory assays Proceedings of the National Academy of Sciences of the United States of America High 19706534
2015 CD19 is required for TLR9-induced B cell activation. TLR9 ligands induce phosphorylation of CD19 through MYD88/PYK2/LYN complexes, which enables recruitment of PI3K and subsequent phosphorylation of Btk and Akt in human B cells with different kinetics than BCR signaling. Loss of one or both CD19 alleles impairs upregulation of CD86, TACI, and CD23 after TLR9 stimulation. CD19-deficient patient B cells (mono- and biallelic mutations); phospho-flow cytometry; immunoblotting; co-immunoprecipitation; lentiviral CD19 knockdown B-cell line; PI3K/AKT/BTK inhibitors The Journal of allergy and clinical immunology High 26478008
2016 Mst1 kinase positively regulates BCR signaling by modulating CD19 transcriptional levels. Mst1 upregulates CD19 mRNA via the transcription factor TEAD2, which directly binds to a consensus motif in the 3' UTR of cd19. Mst1-deficient mice show reduced BCR signaling concurrent with defective BCR clustering and B cell spreading, and defective MZ and germinal center B cell differentiation due to disruption of CD19-mediated Btk signaling. Mst1 knockout mouse model; TIRF microscopy for BCR clustering; chromatin immunoprecipitation/transcription factor binding assay (TEAD2 on cd19 3'UTR); Btk phosphorylation assays Blood advances Medium 29296937
2018 CD19 exon 2 variants generated by in-frame insertions or exon skipping (as resistance mechanisms after CAR T therapy) cause protein misfolding and retention in the endoplasmic reticulum rather than epitope loss per se. CD19 exon 2 variants acquire ER-specific high-mannose glycans but not Golgi-synthesized complex-type glycans, colocalize with ER markers, fail to bind the tetraspanin CD81, and instead interact with ER-resident chaperones (calnexin) and ER transporters. Retroviral transduction and genome editing to generate VSVg-tagged CD19 exon 2 variants; live-cell flow cytometry; pulse-chase glycosylation assays; alpha-mannosidase inhibitor assays; GFP fusion colocalization with ER markers; mass spectrometric profiling of CD19-interacting proteins Molecular and cellular biology High 30104252
2022 Hyperglycosylation of CD19 caused by loss of the Golgi-resident intramembrane protease SPPL3 in malignant B cells directly inhibits CAR T cell effector function and suppresses anti-tumor cytotoxicity, representing a post-translational mechanism of antigen escape. Conversely, over-expression of SPPL3 drives loss of CD19 protein. SPPL3 loss-of-function and overexpression in malignant B cells; in vitro CAR T cell cytotoxicity assays; glycosylation analysis Nature communications Medium 35690611
2023 Cryo-EM structures of CD19 antigen bound to the FMC63 scFv (used in four FDA-approved CAR T therapies) and to SJ25C1 scFv were determined. Molecular dynamics simulations guided by structures enabled creation of lower- or higher-affinity binders. CAR T cells with different affinity binders exhibited distinct antigen density requirements for cytolysis and differed in propensity to trigger trogocytosis upon contacting tumor cells. Cryo-EM structure determination; molecular dynamics simulations; generation of affinity-tuned CAR variants; in vitro CAR T cell cytolysis assays at varying antigen densities; trogocytosis assays Science immunology High 36867678
2019 The FMC63 conformational epitope on the CD19 extracellular domain spans spatially adjacent but genetically distant loops encoded by exons 3 and 4. The epitopes of FMC63, 4G7-2E3, and 3B10 antibodies are partially overlapping but distinct, near the B43 epitope. All N-linked glycosylation sites can be removed from CD19 while retaining antibody binding in a yeast display context. Comprehensive single-site saturation mutagenesis library of CD19 extracellular domain; yeast display; flow cytometric screening for antibody binding; thermal stability selection Biochemistry High 31702909
1999 Enforced CD19 expression in tumorigenic human myeloma cells (which normally lack CD19) inhibits growth in vitro and reduces tumorigenicity in vivo. This growth-inhibitory effect requires the CD19 cytoplasmic signaling domain, as a truncated CD19 lacking this domain does not produce the effect, establishing CD19 signaling as a growth suppressor in myeloma. CD19 transfection of KMS-5 myeloma cell line; in vitro growth and anchorage-independent colony assays; in vivo tumorigenicity in SCID-hIL-6 transgenic mice; truncation mutant controls Blood High 10552966
2014 CD19 deficiency in humans impairs selection of immunoglobulin reactivity in memory B cells. CD19-deficient patients show decreased activation-induced cytidine deaminase and increased uracil-DNA glycosylase 2 activity but decreased mismatch repair during somatic hypermutation, demonstrating a role for CD19 signaling in transcriptional regulation of DNA repair genes during germinal center reactions. CD19-deficient patient samples (n=8); flow cytometry of B cell subsets; molecular analysis of IgA and IgG transcripts; somatic hypermutation analysis; B cell activation studies The Journal of allergy and clinical immunology Medium 24418477
2022 CAR-induced internalization of CD19 is coupled with lysosome-mediated degradation, leading to emergence of transiently CD19-negative leukemic cells that evade CAR T19 immune responses. In contrast, bispecific T-cell engager (STAb-T19) strategy does not induce CD19 downmodulation and forms canonical immunological synapses, preventing this escape mechanism. In vitro coculture of CAR-T19 and STAb-T19 cells with leukemic cells; CD19 surface expression tracking; lysosome inhibitor assays; immunological synapse imaging; in vivo patient-derived xenograft mouse models Cancer immunology research Medium 35362043
2018 Dock8 regulates BCR signaling through CD19. Dock8 deficiency reduces phosphorylated CD19 (pCD19) and phosphorylated Btk (pBtk) levels. WASP positively regulates cd19 transcription, and Dock8 regulates cd19 transcription through WASP. Dock8-deficient B cells show defective BCR clustering and B cell spreading on stimulatory lipid bilayers. Dock8 knockout mouse model; peripheral blood from Dock8-deficient patients; TIRF microscopy; confocal microscopy for BCR clustering/spreading; phospho-flow cytometry for pCD19 and pBtk Blood advances Medium 29472447

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2020 Use of CAR-Transduced Natural Killer Cells in CD19-Positive Lymphoid Tumors. The New England journal of medicine 1730 32023374
2018 Disruption of TET2 promotes the therapeutic efficacy of CD19-targeted T cells. Nature 737 29849141
2016 Dual CD19 and CD123 targeting prevents antigen-loss relapses after CD19-directed immunotherapies. The Journal of clinical investigation 485 27571406
2012 CD19: a biomarker for B cell development, lymphoma diagnosis and therapy. Experimental hematology & oncology 439 23210908
1995 The CD19/CR2/TAPA-1 complex of B lymphocytes: linking natural to acquired immunity. Annual review of immunology 396 7542009
2024 Safety, efficacy and determinants of response of allogeneic CD19-specific CAR-NK cells in CD19+ B cell tumors: a phase 1/2 trial. Nature medicine 394 38238616
1995 CD19 antigen in leukemia and lymphoma diagnosis and immunotherapy. Leukemia & lymphoma 260 8528044
1998 Levels of expression of CD19 and CD20 in chronic B cell leukaemias. Journal of clinical pathology 258 9708202
2000 Quantitative genetic variation in CD19 expression correlates with autoimmunity. Journal of immunology (Baltimore, Md. : 1950) 245 11086109
2016 Catch me if you can: Leukemia Escape after CD19-Directed T Cell Immunotherapies. Computational and structural biotechnology journal 244 27761200
2018 Neurotoxicity Associated with CD19-Targeted CAR-T Cell Therapies. CNS drugs 209 30387077
2015 CAR therapy: the CD19 paradigm. The Journal of clinical investigation 181 26325036
2006 Lineage specification and plasticity in CD19- early B cell precursors. The Journal of experimental medicine 153 16505143
2009 CD19: a promising B cell target for rheumatoid arthritis. Nature reviews. Rheumatology 151 19798033
2020 CART19-BE-01: A Multicenter Trial of ARI-0001 Cell Therapy in Patients with CD19+ Relapsed/Refractory Malignancies. Molecular therapy : the journal of the American Society of Gene Therapy 131 33010231
2011 SAR3419: an anti-CD19-Maytansinoid Immunoconjugate for the treatment of B-cell malignancies. Clinical cancer research : an official journal of the American Association for Cancer Research 128 22003072
2019 Super-resolution microscopy reveals ultra-low CD19 expression on myeloma cells that triggers elimination by CD19 CAR-T. Nature communications 125 31316055
2023 Preinfusion factors impacting relapse immunophenotype following CD19 CAR T cells. Blood advances 120 35482927
2019 Toxicities of CD19 CAR-T cell immunotherapy. American journal of hematology 114 30784102
2017 T-cell receptor αβ+ and CD19+ cell-depleted haploidentical and mismatched hematopoietic stem cell transplantation in primary immune deficiency. The Journal of allergy and clinical immunology 114 28780238
2018 B cell-based therapies in CNS autoimmunity: differentiating CD19 and CD20 as therapeutic targets. Therapeutic advances in neurological disorders 111 29593838
2021 Single-cell profiling identifies pre-existing CD19-negative subclones in a B-ALL patient with CD19-negative relapse after CAR-T therapy. Nature communications 107 33558546
2002 The physiologic role of CD19 cytoplasmic tyrosines. Immunity 105 12387743
2017 CD19 CAR T Cells. Cell 94 29245005
2014 CD19-CAR trials. Cancer journal (Sudbury, Mass.) 94 24667955
1997 CD19 and CD22 expression reciprocally regulates tyrosine phosphorylation of Vav protein during B lymphocyte signaling. Proceedings of the National Academy of Sciences of the United States of America 87 9371816
2001 Cd19-dependent activation of Akt kinase in B-lymphocytes. The Journal of biological chemistry 82 11042164
1998 CD19 regulates B lymphocyte responses to transmembrane signals. Seminars in immunology 80 9695183
2020 Efficacy and safety of CD19 CAR T constructed with a new anti-CD19 chimeric antigen receptor in relapsed or refractory acute lymphoblastic leukemia. Journal of hematology & oncology 78 32894185
2019 Novel CD19-targeted TriKE restores NK cell function and proliferative capacity in CLL. Blood advances 78 30890546
2005 CD19 function in central and peripheral B-cell development. Immunologic research 72 15778510
2012 CD19 as an attractive target for antibody-based therapy. mAbs 70 22820352
2018 CD19 Alterations Emerging after CD19-Directed Immunotherapy Cause Retention of the Misfolded Protein in the Endoplasmic Reticulum. Molecular and cellular biology 69 30104252
2017 CD19, from bench to bedside. Immunology letters 69 28153605
2020 Donor-derived CD19 CAR-T cell therapy of relapse of CD19-positive B-ALL post allotransplant. Leukemia 68 33077866
2003 CD19 function in early and late B cell development. II. CD19 facilitates the pro-B/pre-B transition. Journal of immunology (Baltimore, Md. : 1950) 68 14634103
2001 CD19, CD21, and CD22: multifaceted response regulators of B lymphocyte signal transduction. International reviews of immunology 65 11913948
2022 Antigen glycosylation regulates efficacy of CAR T cells targeting CD19. Nature communications 61 35690611
2020 Mechanisms underlying CD19-positive ALL relapse after anti-CD19 CAR T cell therapy and associated strategies. Biomarker research 59 32514351
2023 CD19 CAR antigen engagement mechanisms and affinity tuning. Science immunology 58 36867678
2021 CAR T cells: Building on the CD19 paradigm. European journal of immunology 56 34196410
2014 Human CD19 and CD40L deficiencies impair antibody selection and differentially affect somatic hypermutation. The Journal of allergy and clinical immunology 54 24418477
2024 Sequential antigen loss and branching evolution in lymphoma after CD19- and CD20-targeted T-cell-redirecting therapy. Blood 52 37976456
2021 CD19 Chimeric Antigen Receptor-Exosome Targets CD19 Positive B-lineage Acute Lymphocytic Leukemia and Induces Cytotoxicity. Cancers 52 33808645
2005 Diminished expression of CD19 in B-cell lymphomas. Cytometry. Part B, Clinical cytometry 49 15624204
2020 Complications after CD19+ CAR T-Cell Therapy. Cancers 47 33228221
2015 CD19 controls Toll-like receptor 9 responses in human B cells. The Journal of allergy and clinical immunology 46 26478008
2014 CD19 and CD32b differentially regulate human B cell responsiveness. Journal of immunology (Baltimore, Md. : 1950) 46 24442430
2018 Genome-wide DNA methylation changes in CD19+ B cells from relapsing-remitting multiple sclerosis patients. Scientific reports 45 30479356
2019 Transcriptome and Regulatory Network Analyses of CD19-CAR-T Immunotherapy for B-ALL. Genomics, proteomics & bioinformatics 44 31201998
2013 Therapeutic targeting of CD19 in hematological malignancies: past, present, future and beyond. Leukemia & lymphoma 42 23885836
2023 Cytokine and reactivity profiles in SLE patients following anti-CD19 CART therapy. Molecular therapy. Methods & clinical development 40 37744005
2024 Aggressive Lymphoma after CD19 CAR T-Cell Therapy. The New England journal of medicine 39 39589371
2021 A novel and efficient tandem CD19- and CD22-directed CAR for B cell ALL. Molecular therapy : the journal of the American Society of Gene Therapy 38 34478871
2015 CD19 CAR Therapy for Acute Lymphoblastic Leukemia. American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Annual Meeting 38 25993197
2002 Complementary roles for CD19 and Bruton's tyrosine kinase in B lymphocyte signal transduction. Journal of immunology (Baltimore, Md. : 1950) 38 12023340
2019 Fine Epitope Mapping of the CD19 Extracellular Domain Promotes Design. Biochemistry 36 31702909
1999 Enforced CD19 expression leads to growth inhibition and reduced tumorigenicity. Blood 36 10552966
2021 Sensitivity and Specificity of CD19.CAR-T Cell Detection by Flow Cytometry and PCR. Cells 35 34831430
2001 A CD19-dependent signaling pathway regulates autoimmunity in Lyn-deficient mice. Journal of immunology (Baltimore, Md. : 1950) 35 11509585
2020 How I treat adults with advanced acute lymphoblastic leukemia eligible for CD19-targeted immunotherapy. Blood 34 31899793
2013 A CD19/Fc fusion protein for detection of anti-CD19 chimeric antigen receptors. Journal of translational medicine 34 23360526
2006 Loss of CD19 expression in B-cell neoplasms. Histopathology 33 16430470
2022 CD34+CD19-CD22+ B-cell progenitors may underlie phenotypic escape in patients treated with CD19-directed therapies. Blood 32 35421218
2009 Uncoupling CD21 and CD19 of the B-cell coreceptor. Proceedings of the National Academy of Sciences of the United States of America 32 19706534
2002 Role of CD19 signal transduction in B cell biology. Immunologic research 32 12403344
2023 Which one is better for refractory/relapsed acute B-cell lymphoblastic leukemia: Single-target (CD19) or dual-target (tandem or sequential CD19/CD22) CAR T-cell therapy? Blood cancer journal 31 37095120
2019 Retargeting CD19 Chimeric Antigen Receptor T Cells via Engineered CD19-Fusion Proteins. Molecular pharmaceutics 31 31242389
2017 CD28 and 41BB Costimulation Enhances the Effector Function of CD19-Specific Engager T Cells. Cancer immunology research 31 28821531
2016 CD19 chimeric antigen receptor (CD19 CAR)-redirected adoptive T-cell immunotherapy for the treatment of relapsed or refractory B-cell Non-Hodgkin's Lymphomas. American journal of cancer research 30 27186412
2023 Dual targeting of CD19 and CD22 against B-ALL using a novel high-sensitivity aCD22 CAR. Molecular therapy : the journal of the American Society of Gene Therapy 29 36945773
2021 HLA-haploidentical TCRαβ+/CD19+-depleted stem cell transplantation in children and young adults with Fanconi anemia. Blood advances 29 33656536
2022 Overcoming CAR-Mediated CD19 Downmodulation and Leukemia Relapse with T Lymphocytes Secreting Anti-CD19 T-cell Engagers. Cancer immunology research 28 35362043
2024 Intratumoral CD38+CD19+B cells associate with poor clinical outcomes and immunosuppression in patients with pancreatic ductal adenocarcinoma. EBioMedicine 26 38608514
2016 Mst1 positively regulates B-cell receptor signaling via CD19 transcriptional levels. Blood advances 26 29296937
2015 BAFF-driven autoimmunity requires CD19 expression. Journal of autoimmunity 26 26103922
2010 B-cell maturation and antibody responses in individuals carrying a mutated CD19 allele. Genes and immunity 26 20445561
2018 CD19-positive antibody-secreting cells provide immune memory. Blood advances 25 30478153
2015 Anti-CD19 Monoclonal Antibodies: a New Approach to Lymphoma Therapy. International journal of molecular and cellular medicine 25 26629482
2013 Targeting CD19 in B-cell lymphoma: emerging role of SAR3419. Cancer management and research 24 24023523
2002 CD19 expression and growth inhibition of tumours in human multiple myeloma. Leukemia & lymphoma 24 12002767
2023 Compromised antigen binding and signaling interfere with bispecific CD19 and CD79a chimeric antigen receptor function. Blood advances 23 36469024
2022 CD19-Targeted Immunotherapies for Diffuse Large B-Cell Lymphoma. Frontiers in immunology 22 35280988
2018 Dock8 regulates BCR signaling and activation of memory B cells via WASP and CD19. Blood advances 22 29472447
2017 Diphtheria toxin-based anti-human CD19 immunotoxin for targeting human CD19+ tumors. Molecular oncology 22 28306193
2022 Developing lisocabtagene maraleucel chimeric antigen receptor T-cell manufacturing for improved process, product quality and consistency across CD19+ hematologic indications. Cytotherapy 21 35610089
2024 CD19 occupancy with tafasitamab increases therapeutic index of CART19 cell therapy and diminishes severity of CRS. Blood 20 37879074
2022 CD19+CD24highCD27+ B cell and interleukin 35 as potential biomarkers of disease activity in systemic lupus erythematosus patients. Advances in rheumatology (London, England) 20 36494762
2023 Anti-CD19 CAR T-cell consolidation therapy combined with CD19+ feeding T cells and TKI for Ph+ acute lymphoblastic leukemia. Blood advances 19 36897251
2023 Incidence of CD19-negative relapse after CD19-targeted immunotherapy in R/R BCP acute lymphoblastic leukemia: a review. Leukemia & lymphoma 18 37526512
2022 Haploidentical Stem Cell Transplantation After TCR-αβ+ and CD19+ Cells Depletion In Children With Congenital Non-Malignant Disease. Transplantation and cellular therapy 18 35405368
2022 Loop CD20/CD19 CAR-T cells eradicate B-cell malignancies efficiently. Science China. Life sciences 18 36251156
2021 Anti-CD19 CAR T cells potently redirected to kill solid tumor cells. PloS one 18 33735268
2019 Decreased number of CD19+CD24hiCD38hi regulatory B cells in Diabetic nephropathy. Molecular immunology 18 31181422
2023 Rational Protein Design Yields a CD20 CAR with Superior Antitumor Efficacy Compared with CD19 CAR. Cancer immunology research 17 36409926
2023 Extracellular Vesicles Expressing CD19 Antigen Improve Expansion and Efficacy of CD19-Targeted CAR-T Cells. International journal of nanomedicine 17 36636644
2020 CD19+CD24hiCD38hi B Cell Dysfunction in Primary Biliary Cholangitis. Mediators of inflammation 17 32104147
2018 MiR-15a/16-1 deficiency induces IL-10-producing CD19+ TIM-1+ cells in tumor microenvironment. Journal of cellular and molecular medicine 17 30467955
2014 CD19 as a molecular target in CNS autoimmunity. Acta neuropathologica 17 24993505
2025 CD19.CAR T-cell-derived extracellular vesicles express CAR and kill leukemic cells, contributing to antineoplastic therapy. Blood advances 16 39903124

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